Porous materials have been increasingly applied to processing of solutions containing biological matter. These processes may involve filtration, clarification, fractionation, pervaporation, reverse osmosis, dialysis, affinity separation, blood oxygenation, or similarly related procedures. A common occurrence in such processes is loss of process efficiency due to fouling of material surfaces by biological matter, and most particularly by proteinaceous matter. Such fouling robs these processes of their efficiency and cost effectiveness, entailing process downtime for cleaning and early replacement of irretrievably fouled portions of porous material components.
Proteinaceous biomolecules are highly complex, containing both hydrophilic and hydrophobic regions. These biomolecules are highly conformable and adaptable toward adsorption to surfaces having hydrophobic moieties thereat. They are inherently surface-active and readily bind to material surfaces at the surface-liquid interface. The problem of uncontrolled adsorption of proteinaceous matter extends through a myriad of processes and applications involving contact or processing of proteinaceous solutions and suspensions.
Ultrafiltration of whey through microporous polysulfone membranes provides a particularly prominent example of this problem. Ulfiltration membranes typically show extremely high throughputs of water when tested on pure water as a process feedstream. Contact with a whey as a process feedstream almost always results in an prompt and drastic decline in flux through the same membrane. Adsorption of proteinaceous matter, particularly beta-lactoglobulin and alpha-lactalbumin, has been identified as a primary contributing cause for such drastic flux declines.
Other examples of deleterious effects of protein adsorption on porous surfaces include: clotting of blood on dialysis and oxygenator membranes and hemolysis of red blood cells on surfaces; loss of costly bioengineered proteins (growth hormones, clotting factors, specialty enzymes, etc.) due to irreversible adsorption onto processing membranes; inability to size-fractionate proteins by filtration due to concomitant adsorption and fouling of filter surfaces by proteinaceous molecules; and high background noise in some types of DNA/polynucleic acid blotting analysis procedures due to generalized adsorption of amino-acid-containing biomolecules including proteins.
It is generally known in the art that hydrophobic materials adsorb protein from aqueous solutions or suspensions. It is also generally known in the art that treatments to increase the hydrophilicity of materials often decrease protein adsorption. As a result, various treatments and approaches have been applied to making porous materials that have hydrophilic surfaces. Included in such approaches are methods employing application of hydrophilic polymer coatings, graft polymerizing hydrophilic monomers onto hydrophobic surfaces, treating hydrophobic surfaces with peroxides to alter surface chemistries, modifying with gas plasmas to alter surface chemistries or deposit hydrophilic plasma polymers, and blending or alloying hydrophilic polymers with hydrophobic polymers in the original preparation of the porous materials. Improvements in resistance to fouling by proteinaceous substances have been achieved in some measure by each of these approaches.
Nevertheless, the problem of protein fouling of porous materials is far from being satisfactorily solved. One of the difficulties inherent in the various approaches is the inconstancy of hydrophilicity as a surface parameter. Yasuda (Plasma Polymerization, Academic Press, Orlando, Fla., 1985, pp. 345-354) has explained that, in polymeric materials, so-called hydrophilic surfaces contain both hydrophilic and hydrophobic molecular components, and that rotational motion inherent in most polymeric surfaces allow movement and orientation of these components so as to provide the lowest possible energy state at an interface of the polymer surface with water, air, or proteinaceous solution. Thus, a hydrogel consisting of as high as 90% water content may still exhibit a hydrophobic surface by reason of orientation of hydrophobic moieties (as evidenced by contact angle measurements), and may show significant adsorption characteristics toward proteinaceous compounds in a solution or suspension in contact with the hydrogel. A very tightly crosslinked polymeric structure having hydrophilic groups on its outer surface showed stable hydrophilicity. This was demonstrated by means of a plasma-polymerized poly(methane) layer treated with oxygen to develop surface hydroxyl groups. Such a coating remained hydrophilic over a 200 day period. In U.S. Pat. Nos. 5,760,100 and 5,789,461, this approach has been utilized as an adjunct post-treatment in the manufacture of soft, wearable contact lenses, wherein the ocular contact surface has been treated with a methane-air mixture to provide improved hydrophilicity.
Many other approaches have been, and continue to be, developed and used to confer hydrophilicity to a material surface, including chemical grafting, chemical oxidation or etching, polymer blending or alloying, application of all sorts of polymeric coatings, and treatment with various surfactants.
A difficulty unappreciated heretofore in this field as it relates to polymeric porous materials, such as for example microfiltration and filtration membranes, is the softness of these materials when produced in their porous state. While the source polymer may be a fine example of a rigid thermoplastic engineering resin in its virgin state, processing of the same source polymer into a porous article results in an article whose surface may be easily marred by almost any kind of rubbing or abrasive contact. This softness appears to account for a portion of the hysteresis commonly observed in porous membrane materials in pressurized filtrative and concentrative applications. Previously observed hysteresis effects in filtrations have long been thought to solely reflect probable surface fouling by organic contaminants. Loss of performance in a biomaterial processing application is herein now recognized to be not solely a problem of biofouling, but also to include contribution of the softness of the porous polymeric structure by surface compaction during the pressure effects of the filtration operations. Thus, an optimum solution to the problem of biofouling of porous materials by proteinaceous matter must also take into consideration the softness and compressibility of porous polymeric materials, particularly as it relates to discriminating layers present in porous articles intended for contact and processing of biological solutions and suspensions.
It is an object of this invention therefore to provide porous materials for processing solutions or suspensions of biomaterials, wherein the porous materials have been hardened or annealed. It is also an object of this invention to render such porous materials less adsorptive to biofoulants, particularly proteinaceous matter. It is a further object of this invention to provide improved porous materials having reduced fouling tendencies when exposed to fluids containing proteinaceous matter, wherein such exposure may include such processes as filtration, clarification, fractionation, pervaporation, reverse osmosis, dialysis, affinity separation, blood oxygenation, or similarly related procedures. These and other objects of the invention will become evident to one skilled in the art by means of the description and claims to follow.